Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine
The nature in which the protecting osmolyte trimethylamine N-oxide (TMAO) and the denaturing osmolyte urea affect protein stability is investigated, simulating a decaalanine peptide model in multiple conformations of the denatured ensemble. Binary solutions of both osmolytes and mixed osmolyte solut...
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| Veröffentlicht in: | Journal of the American Chemical Society 2011-02, Vol.133 (6), p.1849-1858 |
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| container_title | Journal of the American Chemical Society |
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| creator | Kokubo, Hironori Hu, Char Y. Pettitt, B. Montgomery |
| description | The nature in which the protecting osmolyte trimethylamine N-oxide (TMAO) and the denaturing osmolyte urea affect protein stability is investigated, simulating a decaalanine peptide model in multiple conformations of the denatured ensemble. Binary solutions of both osmolytes and mixed osmolyte solutions at physiologically relevant concentrations of 2:1 (urea:TMAO) are studied using standard molecular dynamics simulations and solvation free energy calculations. Component analysis reveals the differences in the importance of the van der Waals (vdW) and electrostatic interactions for protecting and denaturing osmolytes. We find that urea denaturation governed by transfer free energy differences is dominated by vdW attractions, whereas TMAO exerts its effect by causing unfavorable electrostatic interactions both in the binary solution and mixed osmolyte solution. Analysis of the results showed no evidence in the ternary solution of disruption of the correlations among the peptide and osmolytes, nor of significant changes in the strength of the water hydrogen bond network. |
| doi_str_mv | 10.1021/ja1078128 |
| format | Article |
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Montgomery</creator><creatorcontrib>Kokubo, Hironori ; Hu, Char Y. ; Pettitt, B. Montgomery ; Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)</creatorcontrib><description>The nature in which the protecting osmolyte trimethylamine N-oxide (TMAO) and the denaturing osmolyte urea affect protein stability is investigated, simulating a decaalanine peptide model in multiple conformations of the denatured ensemble. Binary solutions of both osmolytes and mixed osmolyte solutions at physiologically relevant concentrations of 2:1 (urea:TMAO) are studied using standard molecular dynamics simulations and solvation free energy calculations. Component analysis reveals the differences in the importance of the van der Waals (vdW) and electrostatic interactions for protecting and denaturing osmolytes. We find that urea denaturation governed by transfer free energy differences is dominated by vdW attractions, whereas TMAO exerts its effect by causing unfavorable electrostatic interactions both in the binary solution and mixed osmolyte solution. 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Montgomery</creatorcontrib><creatorcontrib>Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)</creatorcontrib><title>Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>The nature in which the protecting osmolyte trimethylamine N-oxide (TMAO) and the denaturing osmolyte urea affect protein stability is investigated, simulating a decaalanine peptide model in multiple conformations of the denatured ensemble. Binary solutions of both osmolytes and mixed osmolyte solutions at physiologically relevant concentrations of 2:1 (urea:TMAO) are studied using standard molecular dynamics simulations and solvation free energy calculations. Component analysis reveals the differences in the importance of the van der Waals (vdW) and electrostatic interactions for protecting and denaturing osmolytes. We find that urea denaturation governed by transfer free energy differences is dominated by vdW attractions, whereas TMAO exerts its effect by causing unfavorable electrostatic interactions both in the binary solution and mixed osmolyte solution. Analysis of the results showed no evidence in the ternary solution of disruption of the correlations among the peptide and osmolytes, nor of significant changes in the strength of the water hydrogen bond network.</description><subject>08 HYDROGEN</subject><subject>Alanine - chemistry</subject><subject>ELECTROSTATICS</subject><subject>Environmental Molecular Sciences Laboratory</subject><subject>FREE ENERGY</subject><subject>HYDROGEN</subject><subject>Methylamines - pharmacology</subject><subject>Molecular Dynamics Simulation</subject><subject>Oligopeptides - chemistry</subject><subject>Osmosis - drug effects</subject><subject>PEPTIDES</subject><subject>Protein Denaturation - drug effects</subject><subject>Protein Structure, Secondary</subject><subject>PROTEINS</subject><subject>Solutions</subject><subject>SOLVATION</subject><subject>STABILITY</subject><subject>Thermodynamics</subject><subject>UREA</subject><subject>Urea - pharmacology</subject><subject>WATER</subject><subject>Water - chemistry</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0EFLwzAUB_AgipvTg19AguDBQzVJTZp6k-lUGGzgPJc0fdWMNhlJdti3N6O6k6fHe_z4w_sjdEnJHSWM3q8VJYWkTB6hMeWMZJwycYzGhBCWFVLkI3QWwjqtD0zSUzRilHEiSjJG1RI20TSAp862zvcqGmdVh5ceWvBgNQRsLF6E3nW7CPjDdds9CY945ZUNCeGZB8AvFvyXSdq1-Bm0Up2yxsI5OmlVF-Did07Q5-xlNX3L5ovX9-nTPFN5IWJW5LouVc1ECbqWRJIyXUTRllRySlXZAG8E54zXpCaklkI3rVCi4HnTSspJPkHXQ64L0VRBmwj6WztrQccqlSR5XiZ0OyDtXQjpw2rjTa_8Lok9otWhyWSvBrvZ1j00B_lXXQI3A1A6VGu39am28E_QD2qUeVE</recordid><startdate>20110216</startdate><enddate>20110216</enddate><creator>Kokubo, Hironori</creator><creator>Hu, Char Y.</creator><creator>Pettitt, B. 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Montgomery</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a376t-73cb9ab269ecb8080973c67f918511a9de5d65525b0b00b86cdf6a6753df81503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>08 HYDROGEN</topic><topic>Alanine - chemistry</topic><topic>ELECTROSTATICS</topic><topic>Environmental Molecular Sciences Laboratory</topic><topic>FREE ENERGY</topic><topic>HYDROGEN</topic><topic>Methylamines - pharmacology</topic><topic>Molecular Dynamics Simulation</topic><topic>Oligopeptides - chemistry</topic><topic>Osmosis - drug effects</topic><topic>PEPTIDES</topic><topic>Protein Denaturation - drug effects</topic><topic>Protein Structure, Secondary</topic><topic>PROTEINS</topic><topic>Solutions</topic><topic>SOLVATION</topic><topic>STABILITY</topic><topic>Thermodynamics</topic><topic>UREA</topic><topic>Urea - pharmacology</topic><topic>WATER</topic><topic>Water - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kokubo, Hironori</creatorcontrib><creatorcontrib>Hu, Char Y.</creatorcontrib><creatorcontrib>Pettitt, B. 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Montgomery</au><aucorp>Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2011-02-16</date><risdate>2011</risdate><volume>133</volume><issue>6</issue><spage>1849</spage><epage>1858</epage><pages>1849-1858</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><abstract>The nature in which the protecting osmolyte trimethylamine N-oxide (TMAO) and the denaturing osmolyte urea affect protein stability is investigated, simulating a decaalanine peptide model in multiple conformations of the denatured ensemble. Binary solutions of both osmolytes and mixed osmolyte solutions at physiologically relevant concentrations of 2:1 (urea:TMAO) are studied using standard molecular dynamics simulations and solvation free energy calculations. Component analysis reveals the differences in the importance of the van der Waals (vdW) and electrostatic interactions for protecting and denaturing osmolytes. We find that urea denaturation governed by transfer free energy differences is dominated by vdW attractions, whereas TMAO exerts its effect by causing unfavorable electrostatic interactions both in the binary solution and mixed osmolyte solution. Analysis of the results showed no evidence in the ternary solution of disruption of the correlations among the peptide and osmolytes, nor of significant changes in the strength of the water hydrogen bond network.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>21250690</pmid><doi>10.1021/ja1078128</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 08 HYDROGEN Alanine - chemistry ELECTROSTATICS Environmental Molecular Sciences Laboratory FREE ENERGY HYDROGEN Methylamines - pharmacology Molecular Dynamics Simulation Oligopeptides - chemistry Osmosis - drug effects PEPTIDES Protein Denaturation - drug effects Protein Structure, Secondary PROTEINS Solutions SOLVATION STABILITY Thermodynamics UREA Urea - pharmacology WATER Water - chemistry |
| title | Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine |
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